Nitric Oxide and Hemodynamic Impairment

Groszmann, Roberto J.

doi:10.1159/000051411

Cited by 16 publications

(5 citation statements)

References 9 publications

(8 reference statements)

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“…In addition to the structural alterations, cirrhosis is characterized by an imbalance in vasoactive mediators, indicated by an increase in vasoconstrictors (mainly Endothelin-1) and a decrease in vasodilators (mainly nitric oxide), leading to endothelial dysfunction. As a result of the above-mentioned alterations in cirrhosis, portal hypertension occurs, with the added risk for the development of ascites and esophageal varices [ 3 , 4 , 5 ].…”

Section: Pathogenesis Of Chronic Liver Disease and Cirrhosismentioning

confidence: 99%

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

Hollenbach¹

2017

IJMS

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Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC). AGEs and RAGE are upregulated in liver fibrosis, and the silencing of RAGE reduced collagen deposition and the tumor growth of HCC. Nevertheless, data relating to Glo-I in fibrosis and cirrhosis are preliminary. Glo-I expression was found to be reduced in early and advanced cirrhosis with a subsequent increase of MGO-levels. On the other hand, pharmacological modulation of Glo-I resulted in the reduced activation of hepatic stellate cells and therefore reduced fibrosis in the CCl4-model of cirrhosis. Thus, current research highlighted the Glo-I/AGE/RAGE system as an interesting therapeutic target in chronic liver diseases. These findings need further elucidation in preclinical and clinical studies.

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Section: Pathogenesis Of Chronic Liver Disease and Cirrhosismentioning

confidence: 99%

The Role of Glyoxalase-I (Glo-I), Advanced Glycation Endproducts (AGEs), and Their Receptor (RAGE) in Chronic Liver Disease and Hepatocellular Carcinoma (HCC)

Hollenbach¹

2017

IJMS

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“…The net contractile activity of stellate cells in vivo reflects the relative strength of these opposing factors 98 . In fact, portal hypertension may reflect diminished NO activity, in addition to increased stimulation by ET‐1 106 , 107 …”

Section: Hepatic Stellate Cell Activation: Common Pathway Leading To mentioning

confidence: 99%

Liver fibrogenesis and the role of hepatic stellate cells: New insights and prospects for therapy

Friedman

1999

J of Gastro and Hepatol

318

214

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cation of apoptotic mediators in stellate cells and exploration of their role in clearance of activated stellate cells during the resolution of liver injury.A more comprehensive picture of liver fibrogenesis is thus emerging. This review will emphasize areas of recent progress in understanding liver fibrosis and how these exciting insights will contribute to the generation of effective therapies in the future. EXTRACELLULAR MATRIX: THE MICROENVIRONMENT OF HEPATIC FIBROSIS Extracellular matrix in normal and fibrotic liverThe extracellular matrix refers to the array of macromolecules that comprise the scaffolding of normal and INTRODUCTIONHepatic fibrosis is a wound healing or scarring process which arises in response to liver damage. This response is an attempt to encapsulate injury, but in doing so, liver function is ultimately impaired.The hepatic response to injury represents a paradigm for wound healing in other tissues including skin, lung and kidney, as it involves many of the same cell types and mediators. 1 There has been exciting progress in understanding hepatic fibrosis. Advances have occurred in the following areas: (i) characterization of components of the extracellular matrix (ECM) in normal and fibrotic liver; Department of Medicine and Liver Diseases, Mount Sinai School of Medicine, New York, USAAbstract Hepatic fibrosis is a wound-healing response to chronic liver injury, which if persistent leads to cirrhosis and liver failure. Exciting progress has been made in understanding the mechanisms of hepatic fibrosis. Major advances include: (i) characterization of the components of extracellular matrix (ECM) in normal and fibrotic liver; (ii) identification of hepatic stellate cells as the primary source of ECM in liver fibrosis; (iii) elucidation of key cytokines, their cellular sources, modes of regulation, and signalling pathways involved in liver fibrogenesis; (iv) characterization of key matrix proteases and their inhibitors; (v) identification of apoptotic mediators in stellate cells and exploration of their roles during the resolution of liver injury. These advances have helped delineate a more comprehensive picture of liver fibrosis in which the central event is the activation of stellate cells, a transformation from quiescent vitamin A-rich cells to proliferative, fibrogenic and contractile myofibroblasts. The progress in understanding fibrogenic mechanisms brings the development of effective therapies closer to reality. In the future, targeting of stellate cells and fibrogenic mediators will be a mainstay of antifibrotic therapy. Points of therapeutic intervention may include: (i) removing the injurious stimuli; (ii) suppressing hepatic inflammation; (iii) down-regulating stellate cell activation; and (iv) promoting matrix degradation. The future prospects for effective antifibrotic treatment are more promising than ever for the millions of patients with chronic liver disease worldwide.

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“…Net contractile activity of HSC is determined by the balance between ET-1 and NO. As liver disease progresses, there is increased ET-1 and decreased NO activity [16,[18][19][20].…”

Section: Contractilitymentioning

confidence: 99%